Vitronectin is up-regulated after vascular injury and vitronectin blockade prevents neointima formation

Objective: Smooth muscle cell (SMC) migration involves interactions with extracellular matrix (ECM) and is an important process in response to arterial wall injury. We investigated the expression and the functional role of vitronectin (VN) in the response after vascular injury. Methods: VN and alphavbeta3/beta5 integrin expressions were investigated after balloon carotid injury of Sprague-Dawley rats. Adventitial delivery of blocking antibodies to VN, alphavbeta5 and beta3 integrins were performed to assess their roles in neointima formation. In vitro, migration assays were carried out on human SMC. Results: Immunohistochemistry and in situ hybridization for VN showed an upregulation of VN during the early time points of intima formation. alphavbeta3/beta5 integrins expression correlated with VN expression. After 7 days, blocking antibodies to VN, alphavbeta5 and beta3 induced a significant decrease on intimal area associated with a decrease in intimal cell counts. A slight decrease in intimal cell proliferation without any effect on apoptosis was observed after VN blockade. In vitro, migrating SMC strongly expressed VN after injury and neutralizing anti-VN antibody inhibited SMC migration. Blocking experiment with anti-alphavbeta5 and -alphavbeta3 integrin antibodies showed that not only VN-alphavbeta3 but also VN-alphavbeta5 interactions are required for SMC migration. Conclusion: This study characterizes the VN-ECM interaction in SMC and supports the role of VN in mediating SMC migration and neointimal formation in response to injury. (C) 2002 Elsevier Science BY All rights reserved.